bims-ainimu 2026-01-11 papers

Issue of 2026–01–11
four papers selected by
Pedro Escoll Guerrero, Institut Pasteur

PLoS Biol. 2026 Jan;24(1): e3003585

How do immunometabolites shape bacterial infections?

Metabolites generated by host and pathogen have a major impact on the severity and outcomes of infection. The metabolic response to infection shapes the nature and intensity of the immune response, both in bloodstream infections and, especially, in the pathogenesis of pneumonia. Some metabolites are closely linked to pro-inflammatory responses, whereas others act as immunomodulators in mitigating damage to the host, a common consequence of inflammation. Immunometabolites are also major factors in driving bacterial adaptation to the host, enabling pathogens acquired from environmental sources to modify their gene expression to optimize for persistent infection. In this era of diminishing antimicrobial efficacy, an appreciation of the immunometabolic responses to bacterial infection may provide novel targets for therapy.

DOI: https://doi.org/10.1371/journal.pbio.3003585

Front Immunol. 2025 ;16 1738713

From "metabolic storm" to "immune paralysis": the dynamic evolution of macrophages and metabolism reprogramming in ARDS.

Jia Tang, Mi Yan, Mengchun Li, Zhangxue Hu, Kun Zhou.

Sepsis is characterized by high mortality and a complicated pathological mechanism. Macrophages play a crucial role in the initiation and progression of sepsis-associated acute respiratory distress syndrome (ARDS). Macrophage functional states and polarization phenotype have been significantly influenced by metabolic programming. This review delineates the metabolic reprogramming of macrophages from the initial 'metabolic storm' to subsequent 'immune paralysis' in sepsis-associated ARDS. It focuses on the interplay between macrophage polarization (classical activated macrophages (M1) and alternative activated macrophages (M2) phenotypes) and key metabolic pathways, including glycolysis and oxidative phosphorylation (OXPHOS). Furthermore, it explains the molecular mechanism underlying the metabolic pattern's influence on macrophage and lung tissue damage. The final section of this review focuses on the therapeutic implications of bone marrow mesenchymal stem cells (BMMSCs) and myeloid-derived suppressor cells (MDSCs), which alter macrophage metabolic reprogramming. Based on the latest progress, this article aims to provide a comprehensive theoretical framework and cli Based on recent advances, nical guidance for immunometabolic therapy in sepsis-associated ARDS.

Keywords: ARDS; BMMSCs; exosomes; glycolysis; immune paralysis; macrophage polarization; metabolic reprogramming; metabolic storm

DOI: https://doi.org/10.3389/fimmu.2025.1738713

iScience. 2025 Dec 19. 28(12): 114102

Dual transcriptomic analysis unraveling the immune landscape and host-pathogen interactions during Mycobacterium tuberculosis infection.

Chenyan Shi, Xiaoqian Liu, Dan Chen, Tong Wang, Yu Wang, Ningjian Cai, Zhaodong Li, Yunlong Hu, Yi Cai, Xinchun Chen.

Elucidating the host-pathogen interactions is critical for uncovering the mechanisms controlling Mycobacterium tuberculosis (Mtb) infection. Using dual RNA-seq with fluorescent Mtb, we simultaneously profiled macrophage and bacterial transcriptomes to resolve dynamic intracellular responses. Macrophages containing dead Mtb exhibited strong immune activation, including enhanced antigen presentation and lysosomal function, whereas macrophages harboring live Mtb showed persistent NF-κB signaling and metabolic reprogramming. Mtb counteracted host defenses through upregulation of DNA repair genes and manipulation of extracellular matrix signaling via SPP1 and integrins, alongside tryptophan catabolism and lipid binding pathways supporting adaptation. Cross-species correlation analysis revealed coordinated transcriptional programs, notably a strong inverse association between Mtb aromatic compound catabolism and host receptor tyrosine kinase signaling. Additional correlations linked bacterial metabolism with host lipid transport and steroid biosynthesis. Together, these results provide a high resolution view of macrophage and Mtb transcriptional interplay defining bacterial persistence versus immune clearance.

Keywords: Immunology; Microbiology; Transcriptomics

DOI: https://doi.org/10.1016/j.isci.2025.114102

Int J Mol Sci. 2025 Dec 28. pii: 332. [Epub ahead of print]27(1):

Mitochondrial Transplantation Restores Immune Cell Metabolism in Sepsis: A Metabolomics Study.

Tae Nyoung Chung, Se Rin Choi, Su-Hyun Kim, Choong Hwan Lee, Kyuseok Kim.

Sepsis induces severe immune and metabolic dysfunction driven by mitochondrial failure. Mitochondrial transplantation (MT) has emerged as a promising strategy to restore mitochondrial bioenergetics, but its metabolic impact on immune cells remains unclear. Here, we used gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics to evaluate metabolic alterations in peripheral blood mononuclear cells (PBMCs) and splenocytes from a rat polymicrobial sepsis model treated with MT. Principal component and partial least-squares discriminant analyses revealed distinct clustering between sham, sepsis, and MT groups. Sepsis markedly suppressed metabolites related to amino acid, carbohydrate, and lipid metabolism, including aspartic acid, glutamic acid, AMP, and myo-inositol, reflecting mitochondrial metabolic paralysis. MT partially restored these metabolites toward sham levels, reactivating tricarboxylic acid (TCA) cycle, nucleotide, and lipid pathways. Pathway analysis confirmed that exogenous mitochondria reversed sepsis-induced metabolic suppression and promoted bioenergetic recovery in immune cells. These findings provide direct metabolomic evidence that MT reprograms immune metabolism and restores oxidative and biosynthetic function during sepsis, supporting its potential as a mitochondrial-based metabolic therapy.

Keywords: energy metabolism; gas chromatography–mass spectrometry; immune cells; metabolomics; mitochondrial dysfunction; mitochondrial transplantation; oxidative phosphorylation; peripheral blood mononuclear cells; sepsis; splenocytes

DOI: https://doi.org/10.3390/ijms27010332